HRP members have spent the past three years gathering information about genes that are turned on or off after inner ear hair cell damage in the chick, fish, and mouse. Some of these genes may encode therapeutic agents that can be applied to stimulate hair cell regeneration in humans. Our HRP studies and others have found that five signaling pathways (Wnt, VEGF, BMP4, Notch, and FGF) are important regulators of hair cell regeneration in the chick cochlea (the basilar papilla). The expression and activity of these pathways change significantly after hair cell damage, and the experimental manipulation of activity in each pathway either boosts or dampens hair cell regeneration. Furthermore, each pathway shows distinct regional expression patterns in the basilar papilla, which implicates it in either mitotic regeneration or non-mitotic regeneration—two distinct ways in which hair cells are replaced after damage. Studies in other growing tissues demonstrate that these five pathways regulate one another in temporally and spatially restricted patterns, in order to coordinate cell growth, differentiation, and patterning. Thus, it is likely that any therapy leading to safe and stable hair cell regeneration will require coordinated manipulation of more than one gene or pathway in the cochlea. In this study, we propose to begin to determine how these five powerful pathways interact to enable and control hair cell regeneration in the chick basilar papilla after hair cell damage.